原標(biāo)題：IL-1β可防止小鼠早期鼻病毒感染后IL-2擴(kuò)張、2型細(xì)胞因子分泌和粘液化生
背景：生命早期氣喘相關(guān)性人鼻病毒（RV）呼吸道感染與哮喘的發(fā)展有關(guān)。6日齡未成熟小鼠RV感染可導(dǎo)致粘液化生和氣道高反應(yīng)性，這與產(chǎn)生IL-13的2型固有淋巴細(xì)胞（ILC2s）的擴(kuò)張有關(guān)，并且依賴于IL-25和IL-33。我們檢測了IL-1β對這種哮喘樣表型的調(diào)節(jié)作用。
方法：給6日齡的野生型或NRLP3-/-小鼠接種假手術(shù)或RV-A1B。選擇小鼠接受IL-1受體拮抗劑（IL-1RA），抗IL-1β或重組IL-1β的治療。
結(jié)果：鼻病毒感染引起Il25，Il33，Il4，Il5，Il13，muc5ac和gob5 mRNA表達(dá)，ILC2擴(kuò)增，粘液化生和氣道高反應(yīng)性。RV還誘導(dǎo)肺組織pro-IL-1β和NLRP3的mRNA和蛋白表達(dá)，以及caspase-1和pro-IL-1β的裂解，表明炎癥體的啟動和激活。肺巨噬細(xì)胞是IL-1β的主要來源。用IL-1RA，抗IL-1β或NLRP3 KO抑制IL-1β信號傳導(dǎo)可增加RV誘導(dǎo)的2型細(xì)胞因子免疫反應(yīng)，ILC2數(shù)量和粘液化生，同時降低IL-17 mRNA表達(dá)。IL-1β的治療效果相反，降低IL-25、IL-33和粘液化生，同時增加IL-17的表達(dá)。IL-1β和IL-17各自抑制培養(yǎng)的氣道上皮細(xì)胞中Il25、Il33和muc5ac mRNA的表達(dá)。最后，與成熟小鼠相比，感染RV的6日齡小鼠IL-1β mRNA和蛋白表達(dá)降低。
結(jié)論：巨噬細(xì)胞IL-1β通過抑制上皮細(xì)胞固有細(xì)胞因子的表達(dá)來限制RV感染后的2型炎癥和粘液化生。幼年動物IL-1β分泌減少是早期病毒感染后哮喘發(fā)展的機(jī)制。


延伸閱讀
Allergy                                              
IL‐1β prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early‐life rhinovirus infection in mice
DOI: 10.1111/all.14241
Abstract:
Background: Early‐life wheezing‐associated respiratory infection with human rhinovirus (RV) is associated with asthma development. RV infection of 6‐day‐old immature mice causes mucous metaplasia and airway hyperresponsiveness which is associated with the expansion of IL‐13‐producing type 2 innate lymphoid cells (ILC2s) and dependent on IL‐25 and IL‐33. We examined regulation of this asthma‐like phenotype by IL‐1β.
Methods: Six‐day‐old wild‐type or NRLP3?/? mice were inoculated with sham or RV‐A1B. Selected mice were treated with IL‐1 receptor antagonist (IL‐1RA), anti‐IL‐1β, or recombinant IL‐1β.
Results: Rhinovirus infection induced Il25, Il33, Il4, Il5, Il13, muc5ac, and gob5 mRNA expression, ILC2 expansion, mucus metaplasia, and airway hyperresponsiveness. RV also induced lung mRNA and protein expression of pro‐IL‐1β and NLRP3 as well as cleavage of caspase‐1 and pro‐IL‐1β, indicating inflammasome priming and activation. Lung macrophages were a major source of IL‐1β. Inhibition of IL‐1β signaling with IL‐1RA, anti‐IL‐1β, or NLRP3 KO increased RV‐induced type 2 cytokine immune responses, ILC2 number, and mucus metaplasia, while decreasing IL‐17 mRNA expression. Treatment with IL‐1β had the opposite effect, decreasing IL‐25, IL‐33, and mucous metaplasia while increasing IL‐17 expression. IL‐1β and IL‐17 each suppressed Il25 , Il33, and muc5ac mRNA expression in cultured airway epithelial cells. Finally, RV‐infected 6‐day‐old mice showed reduced IL‐1β mRNA and protein expression compared to mature mice.
Conclusion: Macrophage IL‐1β limits type 2 inflammation and mucous metaplasia following RV infection by suppressing epithelial cell innate cytokine expression. Reduced IL‐1β production in immature animals provides a mechanism permitting asthma development after early‐life viral infection.
First Author:
Mingyuan Han
Correspondence:
Marc B. Hershenson, Departments of Pediatrics, University of Michigan Medical School, Ann Arbor 48109, MI.
All Authors:
Mingyuan Han, Tomoko Ishikawa, Jennifer R. Bermick, Charu Rajput, Jing Lei, Adam M. Goldsmith, Caitlin R. Jarman, Julie Lee, J. Kelley Bentley, Marc B. Hershenson
　　創(chuàng)建過敏性疾病的科研、科普知識交流平臺，為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺。